Whenever a medical device is used in a surgical setting, a risk of infection is created. The risk of infection dramatically increases for invasive or implantable medical devices, such as intravenous catheters, arterial grafts, intrathecal or intracerebral shunts and prosthetic devices, which create a portal of entry for pathogens while in intimate contact with body tissues and fluids. The occurrence of surgical site infections is often associated with bacteria that colonize on the medical device. For example, during a surgical procedure, bacteria from the surrounding atmosphere may enter the surgical site and attach to the medical device. Bacteria can use the implanted medical device as a pathway to surrounding tissue. Such bacterial colonization on the medical device may lead to infection and morbidity and mortality to the patient.
A number of methods for reducing the risk of infection associated with invasive or implantable medical devices have been developed that incorporate antimicrobial agents into the medical devices. Such devices desirably provide effective levels of antimicrobial agent while the device is being used. For example, medical devices may contain antibiotics such as β-lactam antibiotics, polypeptides and quinolones. However, medical devices containing an antibiotic can suffer loss of efficacy resulting from the gradual release of the antibiotic and subsequently, producing sub-lethal concentration of such antibiotic. This sub-lethal concentration of antibiotic would select antibiotic-resistant bacteria. For instance, although β-Lactam antibiotics are known to be efficacious against S. aureus, the bacterial species that is believed to be the most common cause of surgical infections, these antibiotics are ineffective against antibiotic-resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) and MRSE (methicillin-resistant Staphylococcus epidermidis).
One potential solution to this problem is to use a combination of antibiotics and polymeric substrate to immobilize the antibiotics. In particular, it is beneficial if the polymeric substrate is covalently bonded with the antibiotic agent.
US20050192547A1 disclosed an approach for preparing anti-infective polymer-containing medical articles by treatment of the medical articles with a mixed solution of antibiotics and antiseptics. Antimicrobial activities were demonstrated by zone of inhibition (ZOI) experiments. By combination of various antibiotics and antiseptics inhibition to a range of bacteria can be achieved. However, the disclosed approach is solely based on physical absorption or deposition of the agents onto the medical articles. It is obvious that the activity provided is short-termed due to the absence of the covalent bond between the device and the antibiotics. Also, this approach may post potential risk of selecting antibiotic-resistant bacteria.
WO2005016972 A1 describes antimicrobial polymeric materials comprising a polymer linked to a positively charged moiety via a carboxyl group and the processes for the production of such antimicrobial compounds and uses thereof. Once again, the release of antibiotics is not immobilized due to the lack of covalent bonding.
There have been no reports to date on the use of a combination of polysaccharide having covalently bounded antibiotic agents. Therefore, there is a need for polysaccharides having covalently bound antibiotic agents that exhibit sustained and long-term antimicrobial efficacy.